A Novel Approach to Anellated Carbasugar Derivatives, Using Intramolecular 1,3-Dipolar Cycloaddition Reactions of Sugar-Derived Nitrones

Abstract

Intramolecular 1,3‐dipolar cycloaddition of the intermediate nitrones 5 and 6 to double bonds stereoselectively yielded the benzylated anellated carbasugar derivatives 7 and 8. The disaccharide analogue 14 was synthesized similarly. Deprotection afforded the anellated carbasugars 9, 10, and 15, which were investigated as potential inhibitors of glycosidases. This paper also describes the theoretical and experimental evaluation of these compounds as ligands for different enzymes, using automatic docking procedures and enzyme assays, respectively.

Synthesis and Conformational and Biological Aspects of Carbasugars

“…86 The proposed synthesis required the preparation of 5a-carba- Peseke and co-workers have reported an approach to fused carbasugar derivatives, also based on the Ferrier carbocyclization, in which the C 5 branch was incorporated through an intramolecular 1,3-dipolar nitrone cycloaddition (Scheme 178). 400 Cyclitol derivative 1109, readily obtained from 1022 via 1024, 389 was converted to aldehyde 1110 by a carbeneinsertion reaction (ethyl diazocarboxylate, rhodium(II) acetate) followed by reduction (DIBAL-H) of the resulting ester. Treatment of the unstable aldehyde 1110 with either N-benzylhydroxylamine, N-methylhydroxylamine, or methyl 2,3,4-tri-O-benzyl-6-deoxy-6-hydroxyamino-R-D-glucopyranoside hydrochloride in toluene furnished the intermediate nitrones 1111, that underwent spontaneous intramolecular 1,3-dipolar cycloaddition to afford tricyclic derivatives 1112.…”

“…Peseke and co-workers have reported an approach to fused carbasugar derivatives, also based on the Ferrier carbocyclization, in which the C 5 branch was incorporated through an intramolecular 1,3-dipolar nitrone cycloaddition (Scheme ) . Cyclitol derivative 1109 , readily obtained from 1022 via 1024 , was converted to aldehyde 1110 by a carbene-insertion reaction (ethyl diazocarboxylate, rhodium(II) acetate) followed by reduction (DIBAL-H) of the resulting ester.…”

Synthesis and Conformational and Biological Aspects of Carbasugars

“…86 The proposed synthesis required the preparation of 5a-carba- Peseke and co-workers have reported an approach to fused carbasugar derivatives, also based on the Ferrier carbocyclization, in which the C 5 branch was incorporated through an intramolecular 1,3-dipolar nitrone cycloaddition (Scheme 178). 400 Cyclitol derivative 1109, readily obtained from 1022 via 1024, 389 was converted to aldehyde 1110 by a carbeneinsertion reaction (ethyl diazocarboxylate, rhodium(II) acetate) followed by reduction (DIBAL-H) of the resulting ester. Treatment of the unstable aldehyde 1110 with either N-benzylhydroxylamine, N-methylhydroxylamine, or methyl 2,3,4-tri-O-benzyl-6-deoxy-6-hydroxyamino-R-D-glucopyranoside hydrochloride in toluene furnished the intermediate nitrones 1111, that underwent spontaneous intramolecular 1,3-dipolar cycloaddition to afford tricyclic derivatives 1112.…”

“…Peseke and co-workers have reported an approach to fused carbasugar derivatives, also based on the Ferrier carbocyclization, in which the C 5 branch was incorporated through an intramolecular 1,3-dipolar nitrone cycloaddition (Scheme ) . Cyclitol derivative 1109 , readily obtained from 1022 via 1024 , was converted to aldehyde 1110 by a carbene-insertion reaction (ethyl diazocarboxylate, rhodium(II) acetate) followed by reduction (DIBAL-H) of the resulting ester.…”

Synthesis and Conformational and Biological Aspects of Carbasugars

“…86 The proposed synthesis required the preparation of 5a-carba- Peseke and co-workers have reported an approach to fused carbasugar derivatives, also based on the Ferrier carbocyclization, in which the C 5 branch was incorporated through an intramolecular 1,3-dipolar nitrone cycloaddition (Scheme 178). 400 Cyclitol derivative 1109, readily obtained from 1022 via 1024, 389 was converted to aldehyde 1110 by a carbeneinsertion reaction (ethyl diazocarboxylate, rhodium(II) acetate) followed by reduction (DIBAL-H) of the resulting ester. Treatment of the unstable aldehyde 1110 with either N-benzylhydroxylamine, N-methylhydroxylamine, or methyl 2,3,4-tri-O-benzyl-6-deoxy-6-hydroxyamino-R-D-glucopyranoside hydrochloride in toluene furnished the intermediate nitrones 1111, that underwent spontaneous intramolecular 1,3-dipolar cycloaddition to afford tricyclic derivatives 1112.…”

“…Peseke and co-workers have reported an approach to fused carbasugar derivatives, also based on the Ferrier carbocyclization, in which the C 5 branch was incorporated through an intramolecular 1,3-dipolar nitrone cycloaddition (Scheme ) . Cyclitol derivative 1109 , readily obtained from 1022 via 1024 , was converted to aldehyde 1110 by a carbene-insertion reaction (ethyl diazocarboxylate, rhodium(II) acetate) followed by reduction (DIBAL-H) of the resulting ester.…”

Synthesis and Conformational and Biological Aspects of Carbasugars

“…86 The proposed synthesis required the preparation of 5a-carba- Peseke and co-workers have reported an approach to fused carbasugar derivatives, also based on the Ferrier carbocyclization, in which the C 5 branch was incorporated through an intramolecular 1,3-dipolar nitrone cycloaddition (Scheme 178). 400 Cyclitol derivative 1109, readily obtained from 1022 via 1024, 389 was converted to aldehyde 1110 by a carbeneinsertion reaction (ethyl diazocarboxylate, rhodium(II) acetate) followed by reduction (DIBAL-H) of the resulting ester. Treatment of the unstable aldehyde 1110 with either N-benzylhydroxylamine, N-methylhydroxylamine, or methyl 2,3,4-tri-O-benzyl-6-deoxy-6-hydroxyamino-R-D-glucopyranoside hydrochloride in toluene furnished the intermediate nitrones 1111, that underwent spontaneous intramolecular 1,3-dipolar cycloaddition to afford tricyclic derivatives 1112.…”

“…Peseke and co-workers have reported an approach to fused carbasugar derivatives, also based on the Ferrier carbocyclization, in which the C 5 branch was incorporated through an intramolecular 1,3-dipolar nitrone cycloaddition (Scheme ) . Cyclitol derivative 1109 , readily obtained from 1022 via 1024 , was converted to aldehyde 1110 by a carbene-insertion reaction (ethyl diazocarboxylate, rhodium(II) acetate) followed by reduction (DIBAL-H) of the resulting ester.…”